Bladder Cancer, Breast Cancer, Cancer, Colon Cancer, Colorectal Cancer, CRC, EGJ, Esophagogastric Junction Cancer, Gastric Cancer, Head and Neck Cancer, Melanoma, Non Small Cell Lung Cancer, NSCLC, Oncology, Ovarian Cancer, Pancreatic Cancer, Urothelial Cancer
Conditions
Keywords
Cancer, Bi-Sialidase, Anti-Tumor, E-602, Cemiplimab
Brief summary
This is a Phase 1/2, first-in-human, open-label, dose escalation and dose-expansion study of E-602, administered alone and in combination with cemiplimab.
Detailed description
This study is being conducted to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor activity of E-602 in subjects with advanced cancers. Phase 1 of the study consists of dose escalation cohorts of E-602 as a monotherapy and in combination with cemiplimab. Dose escalation will utilize a modified 3+3 design. Any Phase 1 cohort may be backfilled, up to a total of 15 subjects to obtain additional safety, PK, and pharmacodynamic data at a particular dose level. Phase 1 will treat subjects with melanoma, ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer. The safety and pharmacodynamic data will be evaluated to identify the maximum tolerated dose and recommended Phase 2 dose level for E-602 as monotherapy and in combination with cemiplimab. Phase 2 consists of dose-expansion disease cohorts in subjects with 3 types of advanced tumors: melanoma, NSCLC, and a third type to be determined (ovarian, colorectal, pancreatic, breast, gastric/EGJ, head and neck, or urothelial) based on available data. Phase 2 includes cohorts of E-602 as monotherapy and E-602 in combination with cemiplimab. For each cohort in Phase 2, Simon's minimax 2-stage design will be used. The study is seeking to enroll a total of up to 273 subjects (up to 87 in Phase 1 and up to 186 in Phase 2). Subjects will participate in the study for about 16 months.
Interventions
BIOLOGICALE-602
Subjects will receive E-602 (administered weekly, via IV infusion).
BIOLOGICALCemiplimab
Subjects will receive cemiplimab (administered once every 3 weeks, via IV infusion).
Sponsors
Palleon Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1: The study uses a modified 3+3 design with 5 planned dose levels of E-602 as monotherapy and 2 planned dose levels of E-602 in combination with cemiplimab. Phase 2: Consists of dose-expansion and will use the recommended Phase 2 dose level for E-602 as monotherapy and in combination with cemiplimab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Subjects with advanced or relapsed/refractory melanoma, ovarian cancer, NSCLC, colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer who have failed prior therapies. a. Subjects with melanoma, NSCLC, head and neck cancer, urothelial cancer, or mMSI-H or dMMR colorectal cancer must have had prior anti-PD-(L)1 pathway therapy and been deemed resistant (had progression on therapy or within 3 months of discontinuation of therapy). 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3. Subject has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. 4. Adequate bone marrow, coagulation, renal function, and liver function as determined by laboratory tests Key
Exclusion criteria
1. For cohorts receiving E-602 and cemiplimab combination therapy: 1. Prior moderate or severe hypersensitivity to cemiplimab or its formulation 2. History of severe (≥ Grade 3) autoimmune complications or discontinuation due to toxicity following treatment with an anti-PD-(L)1 pathway therapy as a monotherapy, with the exception of asymptomatic Grade 3 elevations in lipase and/or amylase not associated with clinical manifestations of pancreatitis. 3. Subject has an active autoimmune disease. The following are not exclusionary: vitiligo, type 1 diabetes, autoimmune endocrinopathies that are stable on hormone replacement therapy, or psoriasis that does not require systemic treatment. 4. Previously received idelalisib. 2. History of age-related macular degeneration (AMD). 3. Recent surgery, treatment with another investigational agent, active infection, non-healing wound or uncontrolled bleeding/bleeding diathesis. 4. Received a vaccine or prior radiotherapy within 14 days prior to Cycle 1 Day 1. 5. Prior history of interstitial lung disease that required steroids or ≥ Grade 2 immune-related pneumonitis or has current non-infectious pneumonitis or interstitial lung disease. Subject has a history of ≥Grade 3 radiation pneumonitis, or Grade 2 radiation pneumonitis that has been active within the last 6 months. 6. Untreated brain metastases. 7. A known primary malignancy that is progressing or has required active treatment within the past 3 years. 8. Subject is taking the equivalent of \>10 mg/day oral prednisone or on systemic immunosuppressive therapy. 9. Subject has had an allogeneic tissue or organ transplantation. 10. History of thromboembolic event unless the event occurred \> 6 months from Cycle 1 Day 1 and the subject is on anti-coagulation treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced AEs or SAEs | 15 Months | Number of participants who experienced an adverse events (AEs) or a serious adverse event (SAE) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E-602 1 mg/kg Participants received 1 mg/kg E-602 monotherapy administered weekly via IV infusion. | 5 |
| E-602 3 mg/kg Participants received 3 mg/kg E-602 monotherapy administered weekly via IV infusion. | 4 |
| E-602 10 mg/kg Participants received 10 mg/kg E-602 monotherapy administered weekly via IV infusion. | 9 |
| E-602 20 mg/kg Participants received 20 mg/kg E-602 monotherapy administered weekly via IV infusion. | 15 |
| E-602 30 mg/kg Participants received 30 mg/kg E-602 monotherapy administered weekly via IV infusion. | 15 |
| E-602 20 mg/kg in Combination With Cemiplimab Participants received 20 mg/kg E-602 monotherapy administered weekly via IV infusion. They also received 350 mg cemiplimab administered every 3 weeks via IV infusion. | 21 |
| Total | 69 |
Baseline characteristics
| Characteristic | E-602 1 mg/kg | E-602 3 mg/kg | E-602 10 mg/kg | E-602 20 mg/kg | E-602 30 mg/kg | E-602 20 mg/kg in Combination With Cemiplimab | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.0 years STANDARD_DEVIATION 10.79 | 60.0 years STANDARD_DEVIATION 11.17 | 57.9 years STANDARD_DEVIATION 12.39 | 59.1 years STANDARD_DEVIATION 9.36 | 62.1 years STANDARD_DEVIATION 10.25 | 66.5 years STANDARD_DEVIATION 10.31 | 61.7 years STANDARD_DEVIATION 10.67 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 4 Participants | 7 Participants | 11 Participants | 13 Participants | 18 Participants | 56 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 5 Participants | 7 Participants | 7 Participants | 11 Participants | 36 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 4 Participants | 8 Participants | 8 Participants | 10 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 5 | 1 / 4 | 7 / 9 | 9 / 15 | 6 / 15 | 5 / 21 |
| other Total, other adverse events | 5 / 5 | 4 / 4 | 8 / 9 | 15 / 15 | 15 / 15 | 20 / 21 |
| serious Total, serious adverse events | 3 / 5 | 1 / 4 | 1 / 9 | 6 / 15 | 5 / 15 | 5 / 21 |
Outcome results
Primary
Number of Participants Who Experienced AEs or SAEs
Number of participants who experienced an adverse events (AEs) or a serious adverse event (SAE)
Time frame: 15 Months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| E-602 1 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Treatment Emergent AE | 5 Participants |
| E-602 1 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Serious AE | 3 Participants |
| E-602 3 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Treatment Emergent AE | 4 Participants |
| E-602 3 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Serious AE | 1 Participants |
| E-602 10 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Treatment Emergent AE | 8 Participants |
| E-602 10 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Serious AE | 1 Participants |
| E-602 20 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Treatment Emergent AE | 15 Participants |
| E-602 20 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Serious AE | 6 Participants |
| E-602 30 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Treatment Emergent AE | 15 Participants |
| E-602 30 mg/kg | Number of Participants Who Experienced AEs or SAEs | Participants with any Serious AE | 5 Participants |
| E-602 20 mg/kg in Combination With Cemiplimab | Number of Participants Who Experienced AEs or SAEs | Participants with any Treatment Emergent AE | 20 Participants |
| E-602 20 mg/kg in Combination With Cemiplimab | Number of Participants Who Experienced AEs or SAEs | Participants with any Serious AE | 5 Participants |